Current and Emerging Antivirals for the Treatment of Cytomegalovirus (CMV) Retinitis: an Update on Recent Patents

Abstract

Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic complication and a serious cause of vision loss in immunocompromised patients. Even though, a rise in human immunodeficiency virus (HIV) infected individuals seems to be a major factor responsible for the prevalence of CMV retinitis, the introduction of highly active antiretroviral therapy (HAART) significantly reduced the incidence and severity of CMV retinitis. Thorough evaluation of the patient’s immune status and an exact classification of the retinal lesions may provide better understanding of the disease etiology, which would be necessary for optimizing the treatment conditions. Current drugs such as ganciclovir, valganciclovir, cidofovir and foscarnet have been highly active against CMV, but prolonged therapy with these approved drugs is associated with dose-limiting toxicities thus limiting their utility. Moreover development of drug-resistant mutants has been observed particularly in patients with acquired immunodeficiency syndrome (AIDS). Continuous efforts by researchers in the industry and academia have led to the development of newer candidates with enhanced antiviral efficacy and apparently minimal side effects. These novel compounds can suppress viral replication and prevent reactivation in the target population. Though some of the novel therapeutics possess potent viral inhibitory activity, these compounds are still in stages of clinical development and yet to be approved. This review provides an overview of disease etiology, existing anti-CMV drugs, advances in emerging therapeutics in clinical development and related recent patents for the treatment of CMV retinitis.

Cytomegalovirus Retinitis in HIV and Non-HIV Individuals

“…Cytomegalovirus (CMV) is a member of the Herpesviridae family [1,2]. CMV presents as an opportunistic infection in 75-85% of cases; and although infection can occur in healthy individuals, it is uncommon to observe symptomatic CMV infection in individuals who are not immune suppressed [3,4].…”

Treatment of Cytomegalovirus Retinitis With Cytomegalovirus-Specific T-Lymphocyte Infusion

“…3 It is thought that viral particles in the blood enter retinal vascular endothelial cells through endocytosis, resulting ultimately in disruption of the blood-retinal barrier and access thereafter to the retinal tissues. 4-5 CMV retinitis general begins peripherally and spreads centrifugally, with profound visual loss occurring when the infection spreads to the macula or nerve, or when peripheral retinitis leads to a retinal detachment that extends to the macula.…”

“…The CTL line was generated under good manufacturing practice conditions and met clinical release criteria as previously described. 3 The CMVpp65 CTLs were HLA -matched to the recipient and his stem cell donor at 3 of 8 alleles at high resolution and were restricted in their cytotoxicity to CMV epitopes presented by HLA A0201.…”

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

“…(6) [104-105]. This compound was effective against clinical isolates of HSV as well as ACV, CDV, GCV and FOS-resistant isolates of HSV.…”